The High-Throughput Functional Genomics, Proteomics, and Computational Core (referred to as Core B) of this program project proposal has four distinct research support goals that are designed to enable the Individual objectives as described In each project. These research roles are as follows. First, Core B will provide high-throughput mass spectrometry services for the purpose of establishing viral and host protein-protein Interaction maps. Second, Core B will provide advanced computational research support, by bringing modern bioinformatic approaches to protein sequence, structure, and function analysis to bear on the expected deluge of functional data this proposal will generate. Third, Core B will provide leading-edge ultra deep sequencing support to the program project. A major focus of the proposal is the analysis of viral diversity, population structure and plasticity, especially with respect to the evolution of quasi-specles. Ultra deep sequencing (such as that provided by lllumina Solexa technology) allows quantitative and precise measurements of genome-wide genetic dynamics at a depth and accuracy that was unthinkable just a few years ago. The field of deep sequencing, which Includes the methodologies for library generation, the actual sequencing, and the downstream sequence analysis, are rapidly changing. This section of the core will actively research and optimize approaches and Informatics associated with sequencing to support the goals of the program project. Fourth, Core B will provide high-throughput RNAi screening support to the program. In conjunction with the Chandra and Young labs, personnel of Core B will work closely with the Chandra and Young labs for the generation of RNAi libraries and the actual screening.